The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position

Shira Yair-Sabag, Valentina Tedeschi, Carolina Vitulano, Eilon Barnea, Fabian Glaser, Dganit Melamed Kadosh, Joel D. Taurog, Maria Teresa Fiorillo, Rosa Sorrentino, Arie Admon

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the nonassociated HLA-B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2-Lys), in both HLA-B*27:05 and HLA-B*27:09. Furthermore, a small fraction of HLA-B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2-Arg) or the less common glutamine (P2-Gln) located at this anchor position. Overall these data indicate that peptides with P2-Lys should be considered as real ligands of HLA-B*27 molecules and taken into account while looking for putative peptides implicated in the AS.

Original languageEnglish (US)
JournalProteomics
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

HLA-B27 Antigen
HLA-B Antigens
Anchors
Lysine
Ligands
Peptides
Ankylosing Spondylitis
Alleles
Glutamine
Transgenic Rats
Rheumatic Diseases
HeLa Cells
Serine
Cysteine
Arginine
Rats
Spleen
Cells

Keywords

  • 27
  • Ankylosing spondylitis
  • HLA-B
  • Human leukocyte antigen
  • Immunopeptidome
  • Peptidome
  • Transgenic rats

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Yair-Sabag, S., Tedeschi, V., Vitulano, C., Barnea, E., Glaser, F., Melamed Kadosh, D., ... Admon, A. (Accepted/In press). The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position. Proteomics. https://doi.org/10.1002/pmic.201700249

The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position. / Yair-Sabag, Shira; Tedeschi, Valentina; Vitulano, Carolina; Barnea, Eilon; Glaser, Fabian; Melamed Kadosh, Dganit; Taurog, Joel D.; Fiorillo, Maria Teresa; Sorrentino, Rosa; Admon, Arie.

In: Proteomics, 01.01.2018.

Research output: Contribution to journalArticle

Yair-Sabag, S, Tedeschi, V, Vitulano, C, Barnea, E, Glaser, F, Melamed Kadosh, D, Taurog, JD, Fiorillo, MT, Sorrentino, R & Admon, A 2018, 'The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position', Proteomics. https://doi.org/10.1002/pmic.201700249
Yair-Sabag S, Tedeschi V, Vitulano C, Barnea E, Glaser F, Melamed Kadosh D et al. The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position. Proteomics. 2018 Jan 1. https://doi.org/10.1002/pmic.201700249
Yair-Sabag, Shira ; Tedeschi, Valentina ; Vitulano, Carolina ; Barnea, Eilon ; Glaser, Fabian ; Melamed Kadosh, Dganit ; Taurog, Joel D. ; Fiorillo, Maria Teresa ; Sorrentino, Rosa ; Admon, Arie. / The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position. In: Proteomics. 2018.
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abstract = "The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the nonassociated HLA-B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2-Lys), in both HLA-B*27:05 and HLA-B*27:09. Furthermore, a small fraction of HLA-B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2-Arg) or the less common glutamine (P2-Gln) located at this anchor position. Overall these data indicate that peptides with P2-Lys should be considered as real ligands of HLA-B*27 molecules and taken into account while looking for putative peptides implicated in the AS.",
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AU - Glaser, Fabian

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AU - Sorrentino, Rosa

AU - Admon, Arie

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AB - The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the nonassociated HLA-B*27:09 allele, or their cysteine 67 to serine mutants (C67S), are analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S are analyzed from the spleens of rats transgenic for these alleles. The results indicate that C67S mutation increases the percentage of peptides with glutamine or lysine at their P2 position (P2-Lys), in both HLA-B*27:05 and HLA-B*27:09. Furthermore, a small fraction of HLA-B*27 peptides contains lysine at their second position (P2), in addition to the more commonly found peptides with arginine (P2-Arg) or the less common glutamine (P2-Gln) located at this anchor position. Overall these data indicate that peptides with P2-Lys should be considered as real ligands of HLA-B*27 molecules and taken into account while looking for putative peptides implicated in the AS.

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